Structural basis for xenobiotic extrusion by eukaryotic MATE transporter

Mulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics to maintain cellular homeostasis. The human MATE transporters mediate the excretion of xenobiotics and cationic clinical drugs, whereas some plant MATE transporters are responsible for aluminum tolerance and second...

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Published in:Nature communications Vol. 8; no. 1; pp. 1633 - 11
Main Authors: Miyauchi, Hirotake, Moriyama, Satomi, Kusakizako, Tsukasa, Kumazaki, Kaoru, Nakane, Takanori, Yamashita, Keitaro, Hirata, Kunio, Dohmae, Naoshi, Nishizawa, Tomohiro, Ito, Koichi, Miyaji, Takaaki, Moriyama, Yoshinori, Ishitani, Ryuichiro, Nureki, Osamu
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 21.11.2017
Nature Publishing Group
Nature Portfolio
Subjects:
631/45/535/1266
631/45/612/1237
Aluminum
Arabidopsis - chemistry
Arabidopsis - genetics
Arabidopsis - metabolism
Arabidopsis Proteins - chemistry
Arabidopsis Proteins - genetics
Arabidopsis Proteins - metabolism
Biological Transport
Crystal structure
Excretion
Extrusion
Gene Expression Regulation, Plant
Homeostasis
Humanities and Social Sciences
Humans
Hydrogen bonding
Metabolites
multidisciplinary
Organic Cation Transport Proteins - chemistry
Organic Cation Transport Proteins - genetics
Organic Cation Transport Proteins - metabolism
Pharmacokinetics
Pharmacology
Pollution tolerance
Protein Domains
Protonation
Science
Science (multidisciplinary)
Structure-function relationships
Transport
Xenobiotics
Xenobiotics - metabolism
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary:Mulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics to maintain cellular homeostasis. The human MATE transporters mediate the excretion of xenobiotics and cationic clinical drugs, whereas some plant MATE transporters are responsible for aluminum tolerance and secondary metabolite transport. Here we report the crystal structure of the eukaryotic MATE transporter from Arabidopsis thaliana , at 2.6 Å resolution. The structure reveals that its carboxy-terminal lobe (C-lobe) contains an extensive hydrogen-bonding network with well-conserved acidic residues, and their importance is demonstrated by the structure-based mutational analysis. The structural and functional analyses suggest that the transport mechanism involves the structural change of transmembrane helix 7, induced by the formation of a hydrogen-bonding network upon the protonation of the conserved acidic residue in the C-lobe. Our findings provide insights into the transport mechanism of eukaryotic MATE transporters, which is important for the improvement of the pharmacokinetics of the clinical drugs. Mulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics and some plant MATE transporters are involved in secondary metabolite transport. Here, the authors present the structure of the Arabidopsis thaliana MATE transporter AtDTX14 and propose a model for eukaryotic MATE transport mechanism.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01541-0